Repository of Research and Investigative Information

Repository of Research and Investigative Information

Ilam University of Medical Sciences

The key role of Akt protein kinase in metabolic-inflammatory pathways cross-talk: TNF-alpha down-regulation and improving of insulin resistance in HepG2 cell line

Mon Sep 26 13:15:06 2022

(2020) The key role of Akt protein kinase in metabolic-inflammatory pathways cross-talk: TNF-alpha down-regulation and improving of insulin resistance in HepG2 cell line. Current molecular medicine. ISSN 1875-5666 (Electronic) 1566-5240 (Linking)

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Official URL: https://www.ncbi.nlm.nih.gov/pubmed/32338219

Abstract

BACKGROUND: Elevation of plasma free fatty acids as a principal aspect of type 2 diabetes maintains etiologically insulin insensitivity in target cells. TNF-alpha inhibitory effects on key insulin signaling pathway elements remain to be verified in insulin-resistant hepatic cells. Thus, TNF-alpha knockdown effects on the key elements of insulin signaling were investigated in the palmitate-induced insulin-resistant hepatocytes. The Akt serine kinase, a key protein of the insulin signaling pathway, phosphorylation was monitored to understand the TNF-alpha effect on probable enhancing of insulin resistance. METHODS: Insulin-resistant HepG2 cells were produced using 0.5 mM palmitate treatment and shRNA-mediated TNF-alpha gene knockdown and its down-regulation confirmed using ELISA technique. Western blotting analysis used to assess the Akt protein phosphorylation status. RESULTS: Palmitate-induced insulin resistance caused TNF-alpha protein overexpression 1.2-, 2.78, and 2.25- fold as compared to the control cells at post-treatment times of 8 h, 16 h, and 24 h, respectively. In the presence of palmitate, TNF-alpha expression showed around 30 reduction in TNF-alpha knockdown cells as compared to normal cells. In the TNF-alpha down-regulated cell, Akt phosphorylation was approximately 62 more than control cells after treatment with 100 nM insulin in conjugation with 0.5 mM palmitate. CONCLUSIONS: The obtained data demonstrated that TNF-alpha protein expression reduction improved insulin-stimulated Akt phosphorylation in the HepG2 cells and decreased lipid-induced insulin resistance of the diabetic hepatocytes.

Item Type: Article
Creators:
CreatorsEmail
Alipourfard, I.UNSPECIFIED
Bakhtiyari, S.UNSPECIFIED
Gheysarzadeh, A.UNSPECIFIED
Di Renzo, L.UNSPECIFIED
De Lorenzo, A.UNSPECIFIED
Mikeladze, D.UNSPECIFIED
Khamoushi, A.UNSPECIFIED
Keywords: Akt kinase HepG2 cell Insulin resistance Palmitate TNF-alpha diabetes
Divisions:
Journal or Publication Title: Current molecular medicine
Journal Index: Pubmed
Identification Number: https://doi.org/10.2174/1566524020666200427102209
ISSN: 1875-5666 (Electronic) 1566-5240 (Linking)
Depositing User: مهندس مهدی شریفی
URI: http://eprints.medilam.ac.ir/id/eprint/2803

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